Single cells RNA sequencing of peripheral blood mononuclear cells reveals hyperinflammatory monocytes in patients with Mycobaterium abscessus pulmonary disease
F Di Marco(1) S de Pretis(2) A Gramegna(3) F Saliu(1) F Giannese(2) F Blasi(3) D M Cirillo(1) N I Lorè(1)
1:San Raffaele Scientific Institute, Emerging Bacterial Pathogens Unit; 2:San Raffaele Scientific Institute, Center for Omics Sciences; 3:Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Respiratory Unit and Cystic Fibrosis Adult Center
People colonized by M. abscessus (MABSC) such as patients with cystic fibrosis (pwCF) are at risk of developing MABSC Pulmonary Disease (MABSC -PD), which can result in varying clinical outcomes. To improve the clinical management of MABS-PD, there is a need for reliable biomarkers such as immune signatures. In our study, we collected blood samples from adult pwCF and divided them into three groups based on their infection status and clinical stability: pwCF with no history of NTM detection and clinically stable (CF); pwCF NTM-colonized (MABSC); pwCF with clinical diagnosis for pulmonary disease (MABSC-PD). We then performed single cell RNA sequencing and Luminex assays on isolated PBMCs and plasma to identify transcriptomic/molecular signatures characterizing NTM-PD. We found alterations in several cell types, with the most interesting changes occurring in classical monocyte cells in MABSC-PD compared to CF or MABSC groups. Our analysis identified a unique RNA signature consisting of 47 upregulated and 24 downregulated genes. In plasma, CXCL10 levels were significantly higher in MABSC-PD than in other groups among 23 proinflammatory cytokines. Moreover, we validated our cellular target in a second public available datasets from a cohort of CF patients infected by M. abscessus. Our results suggest that hyperinflammatory monocyte responses are present in pwCF at risk of developing MABSC-PD.
Supported by the Italian CF Foundation FFC#23/2020 and FFC#7/2020